{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T03:03:51Z","timestamp":1778900631991,"version":"3.51.4"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2018,7,1]],"date-time":"2018-07-01T00:00:00Z","timestamp":1530403200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100004326","name":"Bayer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The role of inhalational combination therapy when treating carbapenem-resistant\n            <jats:named-content content-type=\"genus-species\">Pseudomonas aeruginosa<\/jats:named-content>\n            and\n            <jats:named-content content-type=\"genus-species\">Klebsiella pneumoniae<\/jats:named-content>\n            with newer beta-lactam\/beta-lactamase inhibitors has not been established. Using a 72-h\n            <jats:italic>in vitro<\/jats:italic>\n            pharmacodynamic chemostat model, we simulated the human exposures achieved in epithelial lining fluid (ELF) following intravenous treatment with ceftazidime-avibactam (CZA) 2.5 g every 8 h (q8h) alone and in combination with inhaled amikacin (AMK-I) 400 mg q12h, a reformulated aminoglycoside designed for inhalational administration, against three\n            <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n            isolates (CZA [ceftazidime\/avibactam] MICs, 4\/4 to 8\/4 \u03bcg\/ml; AMK-I MICs, 8 to 64 \u03bcg\/ml) and three\n            <jats:named-content content-type=\"genus-species\">K. pneumoniae<\/jats:named-content>\n            isolates (CZA MICs, 1\/4 to 8\/4 \u03bcg\/ml; AMK-I MICs, 32 to 64 \u03bcg\/ml). Combination therapy resulted in a significant reduction in 72-h CFU compared with that of CZA monotherapy against two of three\n            <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n            isolates (\u22124.14 log\n            <jats:sub>10<\/jats:sub>\n            CFU\/ml,\n            <jats:italic>P<\/jats:italic>\n            = 0.027; \u22121.42 log\n            <jats:sub>10<\/jats:sub>\n            CFU\/ml,\n            <jats:italic>P<\/jats:italic>\n            = 0.020; and \u22120.4 log\n            <jats:sub>10<\/jats:sub>\n            CFU\/ml,\n            <jats:italic>P<\/jats:italic>\n            = 0.298) and two of three\n            <jats:named-content content-type=\"genus-species\">K. pneumoniae<\/jats:named-content>\n            isolates (0.04 log\n            <jats:sub>10<\/jats:sub>\n            CFU\/ml,\n            <jats:italic>P<\/jats:italic>\n            = 0.963; \u22124.34 log\n            <jats:sub>10<\/jats:sub>\n            CFU\/ml,\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.001; and \u22122.34 log\n            <jats:sub>10<\/jats:sub>\n            CFU\/ml,\n            <jats:italic>P<\/jats:italic>\n            = 0.021). When measured by the area under the bacterial growth curve (AUBC) over 72 h, significant reductions were observed in favor of the combination regimen against all six isolates tested. AMK-I combination therapy successfully suppressed CZA resistance development in one\n            <jats:named-content content-type=\"genus-species\">K. pneumoniae<\/jats:named-content>\n            isolate harboring\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>KPC-3<\/jats:sub>\n            that was observed during CZA monotherapy. These studies suggest a beneficial role for combination therapy with intravenous CZA and inhaled AMK when treating pneumonia caused by carbapenem-resistant Gram-negative bacteria.\n          <\/jats:p>","DOI":"10.1128\/aac.00113-18","type":"journal-article","created":{"date-parts":[[2018,6,13]],"date-time":"2018-06-13T09:49:23Z","timestamp":1528883363000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["Antibacterial Activity of Human Simulated Epithelial Lining Fluid Concentrations of Ceftazidime-Avibactam Alone or in Combination with Amikacin Inhale (BAY41-6551) against Carbapenem-Resistant Pseudomonas aeruginosa and Klebsiella pneumoniae"],"prefix":"10.1128","volume":"62","author":[{"given":"Safa S.","family":"Almarzoky Abuhussain","sequence":"first","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"},{"name":"Umm Al-Qura University, Makkah, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph L.","family":"Kuti","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David P.","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"},{"name":"Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw504"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1080\/14787210.2017.1250625"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/cc13775"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00051-05"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(13)70081-1"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02083-16"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/595011"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1622"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30747-8"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00449-17"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00883-17"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2017.08.030"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkv170"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13613-016-0140-x"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/cc8206"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1089\/jamp.2010.0860"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1586\/17434440.5.1.9"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkv370"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw636"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02097-16"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2015.05.501"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00851-12"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx537"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1089\/mdr.2016.0293"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx419"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu237"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00198-18"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00537-17"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02177-15"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02231-15"},{"key":"e_1_3_2_32_2","volume-title":"Population pharmacokinetic modeling of ceftazidime and avibactam and probability of target attainment to support the dosing regimen in patients with nosocomial pneumonia including ventilator-associated pneumonia","author":"Li J","year":"2015","unstructured":"Li J, Nichols WW, Zhou D, Das S. 2015. Population pharmacokinetic modeling of ceftazidime and avibactam and probability of target attainment to support the dosing regimen in patients with nosocomial pneumonia including ventilator-associated pneumonia, abstr P1289. 25th Eur Congr Clin Microbiol Infect Dis, 25 to 28 April 2015, Copenhagen, Denmark."},{"key":"e_1_3_2_33_2","volume-title":"Document M07-A10","author":"Clinical and Laboratory Standards Institute","year":"2015","unstructured":"Clinical and Laboratory Standards Institute. 2015. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standards, 10th ed. Document M07-A10. 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